Preclinical Studies with MyoKardia’s Mavacamten Demonstrate Evidence of Reduced Contractility and Improved Left Ventricular...
November 15 2017 - 8:00AM
MyoKardia, Inc. (Nasdaq:MYOK), a clinical-stage biopharmaceutical
company pioneering a precision medicine approach for the treatment
of heritable cardiovascular diseases, presented data that further
elucidates the mechanism of action of the company’s lead drug
candidate, mavacamten (formerly MYK-461) at this week’s American
Heart Association (AHA) Scientific Sessions. Data from
MyoKardia’s in vivo study demonstrated that treatment with
mavacamten improved myocardial compliance while preserving systemic
pressures. Mavacamten is an investigational agent that has
been shown in clinical studies to modulate cardiac myosin to reduce
the excess contractility characteristic of hypertrophic
cardiomyopathy (HCM). HCM is a severe and progressive genetic
condition in which the walls of the heart thicken and can obstruct
blood flow from the left ventricle. The thickened heart
muscle is less compliant than normal and therefore fills with less
blood, reducing cardiac output.
“The observation that mavacamten may improve distensibility
while reducing contractility increases our understanding of
mavacamten’s mechanism of action and hemodynamic effects,” said
Robert McDowell, Ph.D., Chief Scientific Officer of
MyoKardia. “We look forward to potentially verifying the
clinical implications of this early evidence of improved myocardial
relaxation and of a rightward shift in the diastolic
pressure-volume relationship, as it could greatly inform
MyoKardia’s ongoing research to address diseases of impaired
diastolic function.”
In healthy animals, the pharmacodynamic effect of mavacamten was
compared to that of metoprolol, a beta blocker commonly prescribed
in the management of HCM, in an acute setting. Mavacamten
reduced systolic performance and increased end diastolic volume
(EDV) while preserving end diastolic pressures (EDP) and systemic
blood pressure. By contrast, metoprolol, at matched levels of
negative systolic performance, caused increased EDP with
significantly less increase in EDV. Chronic treatment with
mavacamten over a nine-month period showed a comparable profile,
characterized by preserved echocardiographic indices of diastole
and filling pressure. Taken together, these data indicate a
distinct and unique mode of action for mavacamten, providing
evidence of improved left ventricular compliance that accompanies
reduced myocardial contractility.
The presentation detailing these results, In Vivo Cardiac
Effects of Mavacamten (MYK-461): Evidence for Negative Inotropy and
Improved Compliance (#405), was part of the Drug Discovery for
Heart Failure session.
About Mavacamten (MYK-461) Mavacamten is a
novel, oral, allosteric modulator of cardiac myosin that reduced
hypercontractility in a Phase 1 clinical study of hypertrophic
cardiomyopathy (HCM) patients. MyoKardia has evaluated mavacamten
in multiple Phase 1 clinical studies, primarily designed to
evaluate safety and tolerability of oral doses of mavacamten, and
provide pharmacokinetic and pharmacodynamic data. In April 2016,
the U.S. FDA granted Orphan Drug Designation for mavacamten for the
treatment of symptomatic oHCM, a subset of HCM. MyoKardia is
currently studying mavacamten in the Phase 2 PIONEER-HCM study.
About MyoKardiaMyoKardia is a clinical-stage
biopharmaceutical company pioneering a precision medicine approach
to discover, develop and commercialize targeted therapies for the
treatment of serious and rare cardiovascular diseases.
MyoKardia’s initial focus is on the treatment of heritable
cardiomyopathies, a group of rare, genetically-driven forms of
heart failure that result from biomechanical defects in cardiac
muscle contraction. MyoKardia has used its precision medicine
platform to generate a pipeline of therapeutic programs for the
chronic treatment of the two most prevalent forms of heritable
cardiomyopathy—hypertrophic cardiomyopathy (HCM), and dilated
cardiomyopathy (DCM). MyoKardia’s most advanced product candidate
is mavacamten (formerly MYK-461), a novel, oral, allosteric
modulator of cardiac myosin that has been shown to reduce
hypercontractility in early clinical studies and is currently being
studied in the Phase 2 PIONEER-HCM clinical trial. MYK-491,
MyoKardia’s second product candidate, is designed to increase the
overall extent of the heart’s contraction in DCM patients by
increasing cardiac contractility. MyoKardia is currently evaluating
MYK-491 in a Phase 1 study in healthy volunteers. A cornerstone of
the MyoKardia platform is the Sarcomeric Human Cardiomyopathy
Registry (SHaRe), a multi-center, international repository of
clinical and laboratory data on individuals and families with
genetic heart disease, which MyoKardia helped form in 2014.
MyoKardia’s mission is to change the world for patients with
serious cardiovascular disease through bold and innovative
science.
Contacts
Beth DelGiacco (Investors)Stern Investor Relations, Inc.
212-362-1200 beth@sternir.com
Steven Cooper (Media)Edelman 415-486-3264
steven.cooper@edelman.com
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